Sentinel variant vs lead variant vs top variant vs index variant¶
In GWAS and QTL usage, these terms usually refer to the strongest associated variant for a locus-level signal. The difference is mostly wording and emphasis: top variant is informal, lead variant is the common formal term, and sentinel variant / index variant emphasize the representative marker used to index that signal.
How they differ¶
| Top variant | Lead variant | Sentinel variant | Index variant | |
|---|---|---|---|---|
| Typical tone | Informal wording in slides, captions, quick summaries. | Most common formal wording in GWAS papers and catalogs. | Formal wording emphasizing representative/index marker role. | Formal workflow/reporting wording in pipelines and catalogs. |
| Usual statistical meaning | Smallest p-value in the region or analysis window. | Primary association variant for a signal/locus. | Representative variant for the locus signal, often also the smallest p-value in the region. | Representative variant chosen to index one signal/locus, often equivalent to lead/sentinel in practice. |
| What it implies | "Best hit" by ranking. | "Main reported hit" for that signal. | "Tagging/indexing marker" for downstream reporting and follow-up. | "Anchor ID per signal" for clumping, annotation, and reporting tables. |
Rule of thumb: In most GWAS/QTL papers these terms point to the same statistical variant; the preferred wording changes by author, field, journal style, and analysis pipeline conventions.
Important caveat¶
The lead/sentinel/top/index variant is not always the causal variant. It can be the strongest statistical proxy because nearby variants are correlated through linkage disequilibrium (LD). Follow-up methods (e.g. fine-mapping, conditional association analysis, and functional assays) are needed to narrow causal candidates.
Related terms¶
- Index Variant
- Locus
- Linkage Disequilibrium (LD)
- Regional Plot
- Fine-Mapping
- Conditional Association Analysis
References¶
- Uffelmann E, et al. (2021). Genome-wide association studies. Nat Rev Methods Primers. https://doi.org/10.1038/s43586-021-00056-9
- Buniello A, et al. (2019). The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res. https://doi.org/10.1093/nar/gky1120